5: Chronic complications

Published on 26/02/2015 by admin

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Section 5 Chronic complications

Ocular complications

Clinically significant ocular complications associated with diabetes include:

Diabetic retinopathy

Diabetic retinal disease is the commonest cause of visual impairment in patients with type 1 diabetes. Diabetic retinopathy is more than likely to occur in patients who have poorly controlled diabetes and its prevalence increases with the duration of diabetes. Fifty per cent of patients with type 1 diabetes will have some form of retinopathy after 10 years. Approximately 5–10% of patients with type 2 diabetes will present with retinopathy (with a small number having sight-threatening retinopathy).

The following risk factors have been shown to determine the development and progression of diabetic retinal disease:

Clinically significant macular oedema and hard exudate formation but not proliferative retinopathy or retinopathy progression appears to be associated with total, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol levels.

Patients with multiple risk factors should be considered at particularly high risk of developing diabetic retinal disease.

No features ≤ 2 disc diameters from the centre of the fovea sufficient to qualify for M1 or M2 as defined below.

PHOTOCOAGULATION (P) OTHER LESIONS (OL) Other non-diabetic lesions present:

IRMA, intraretinal microvascular anomaly.

Another commonly used grading system is the Early Treatment Diabetic Retinopathy Study (ETDRS) system (Table 5.2).

Table 5.2 The Early Treatment Diabetic Retinopathy Study (ETDRS) system

Grade Features
None Normal retina
Early Microaneurysms only
Mild Microaneurysms plus:
Moderate Mild; NPDR plus:
Severe Moderate NPDR plus 4/2/1 rule:
Very severe Any two or more of the ‘severe categories’
PDR without HRC NVE or NVD < ½DD
PDR with HRC NVE or NVD > ½DD plus preretinal and/or vitreous haemorrhages

DD, disc diameter; HRC, high-risk changes; IRMA, intraretinal microvascular anomaly; NPDR, non-proliferative diabetic retinopathy; NVD, new vessels on the disc; NVE, new vessels elsewhere in the retina; PDR, proliferative diabetic retinopathy.


Diabetic retinopathy can progress significantly without the patient being aware of any problems. The primary aim of screening is the detection of potentially sight-threatening retinopathy in asymptomatic people so that treatment, where required, can be performed before visual impairment occurs.

Retinal screening is defined as the ongoing assessment of fundi with no diabetic retinopathy or non-sight-threatening diabetic retinopathy. Once sight-threatening eye disease develops, treatment is usually required. Diabetic retinopathy screening does not remove the need for a regular general eye examination to monitor changes in refraction and to detect other eye disease.

In patients with type 1 diabetes it takes 5–6 years for retinopathy to progress. In type 1 patients aged 11 years or older, it can take 1–2 years for retinopathy to progress. A population-based study demonstrated the prevalence of retinopathy to be 14.5% for any retinopathy and 2.3% for proliferative and pre-proliferative retinopathy in children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15 years and who were older than 9 years at the time of examination. Pre-proliferative retinopathy has been identified as early as 3.5 years after diagnosis in patients postpuberty, and within 2 months of onset of puberty.

General principles of management of diabetic retinopathy

Proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) affects about 5 –10% of the diabetic population and is more common in type 1 diabetes.

Neovascularization is the hallmark of PDR. New vessels are commonly seen along the retinal arcades, but can occur at the optic disc or elsewhere in the retina. As a general rule, the retina distal to the neovascularization should be considered as ischaemic, and it has been estimated that more than one-quarter of the retina has to be non-perfused before neovascularization occurs. Ischaemia upregulates the vascular endothelial growth factor (VEGF) that stimulates neovascularization. New vessels start as endothelial proliferations, and pass through the internal limiting membrane to lie in the potential plane between the retina and the posterior vitreous face. PDR can result in visual deterioration from ischaemia, haemorrhage and tractional retinal detachment involving the macula (Table 5.4).

Table 5.4 Guidelines for referral for specialist assessment of diabetic retinopathy

Clinical problem Urgency (within)
Sudden loss of vision 1 day
Evidence of retinal detachment 1 day
New vessel formation (on the disc or elsewhere) 1 week
Vitreous or pre-retinal haemorrhage 1 week
Rubeosis iridis 1 week
Hard exudates within 1DD of the fovea or clinically significant macular oedema 4 weeks
Unexplained drop in visual acuity 4 weeks
Unexplained retinal findings 4 weeks
Severe or very severe non-proliferative retinopathy is present 4 weeks

Laser photocoagulation

The efficacy of photocoagulation has been demonstrated in the Diabetic Retinopathy Study (DRS) and ETDRS studies. It is believed that the regression of neovascularization is due to the destruction of ischaemic and hypoxic retina with the reduction in angiogenic factors.

Panretinal photocoagulation is now the main modality of treatment for proliferative diabetic retinopathy and severe non-proliferative diabetic retinopathy (NPDR). Clinically significant macular oedema (CSMO) can be treated with focal or grid photocoagulation.

Panretinal laser involves the application of 500 μm of Argon laser photocoagulation spots, each separated by an interval of a similar spot size to the mid-peripheral retina. A row of laser burns are initially placed approximately three disc diameters temporal to the fovea to avoid getting closer to the fovea. About 1500 burns are usually required (in two to three sessions). Severe cases may require further photocoagulation. The aim is to cover the ischaemic areas and regression of new vessels occurs in almost 80% of cases. Fundus fluorescein angiography (FFA) should be undertaken initially to delineate the ischaemic areas, or should be done to ensure coverage of ischaemic areas with laser if good regression of neovascularization is not achieved even with initial retinal photocoagulation.

Laser treatment can be associated with pain, transient visual loss, loss of visual field (inevitable) and, sometimes, reduced visual acuity and choroidal damage.

In very aggressive cases of PDR, an intravitreal injection of an anti-VEGF can give a valuable window period until the laser photocoagulation takes effect which can take up to 2 weeks.

Pharmacological therapy

Fenofibrate reduces the risk of progression of retinopathy and the need for laser treatment in patients with type 2 diabetes. The outcomes were not explained by a change in the serum lipid profile and the effect was independent of its lipid-lowering properties.

Intravitreal triamcinolone may provide a short-term reduction in retinal thickness and a corresponding improvement in visual acuity. In the long term it does not appear to have any benefit over laser treatment. Triamcinolone may be useful in patients who do not respond to laser. There is a risk of raising intraocular pressure: in one study, 68% of patients were affected, with 44% requiring glaucoma medication and 54% of patients requiring cataract surgery.

A randomized clinical trial of patients with type 2 diabetes and raised serum lipid levels at baseline, found that atorvastatin reduced the severity of hard exudates following laser therapy (P  =  0.007), although the clinical significance of this is not certain. A similar study showed a non-statistically significant improvement in visual acuity and reduction in clinically significant macular oedema in patients on simvastatin.

There is insufficient evidence to warrant routine usage of anti-VEGF therapies for the treatment of proliferative diabetic retinopathy or diabetic macular oedema, either as stand-alone therapy or as an adjuvant to laser therapy.

There is no good evidence for any additional benefit of angiotensin converting enzyme (ACE) inhibitors in diabetic eye disease.

An angiotensin receptor blocker (ARB) appeared to reduce significantly the incidence of new-onset retinopathy in patients with type 1 diabetes, by 35% when measured as a change of three steps in the ETDRS scale, rather than the two steps in the original study design. Treatment with the ARB enhanced regression of retinopathy by 34% in patients with type 2 diabetes with early retinopathy.

Diabetic neuropathy

The wide variability in symmetrical diabetic polyneuropathy prevalence data is due to lack of consistent criteria for diagnosis, variable methods of selecting patients for study, and differing assessment techniques. In addition, because many patients with diabetic polyneuropathy are initially asymptomatic, detection is extremely dependent on careful neurological examination by the primary care clinician.

In the UK, the prevalence of diabetic neuropathy among the hospital clinic population is thought to be around 30%. Using additional methods of detection, such as autonomic or quantitative sensory testing, the prevalence may be higher.

Classification of neuropathy

A generally accepted classification of peripheral diabetic neuropathies divides them broadly into symmetrical and asymmetrical neuropathies. Development of symptoms depends on total hyperglycaemic exposure plus other risk factors such as raised lipid levels, BP, smoking, and high exposure to other potentially neurotoxic agents such as ethanol. Establishing the diagnosis requires careful evaluation, as patients with diabetes may present with a neuropathy from another cause.

Symmetrical polyneuropathies

Symmetrical polyneuropathies involve multiple nerves diffusely and symmetrically:

Distal symmetrical polyneuropathy:

Small-fibre neuropathy:

Diabetic autonomic neuropathy:

Diabetic neuropathic cachexia:

Asymmetrical neuropathies

Asymmetrical neuropathies include single or multiple cranial or somatic mononeuropathies. Syndromes include median neuropathy of the wrist (carpal tunnel syndrome), single or multiple somatic mononeuropathies, thoracic radiculoneuropathy, lumbosacral radiculoplexus neuropathy and cervical radiculoplexus neuropathy. These syndromes usually have a monophasic course, may appear acutely or subacutely, and have a weaker association with glycaemic control than symmetrical polyneuropathies.

Cranial mononeuropathy:

Somatic mononeuropathies:

Diabetic thoracic radiculoneuropathy:

Diabetic radiculoplexus neuropathy:

Physical signs

The clinical signs and symptoms are usually in keeping with where the neuropathy fits into the classification described above.

Distal symmetrical sensorimotor polyneuropathy due to diabetes must occur in the presence of diabetes as outlined by the American Diabetes Association or World Health Organization. The severity of polyneuropathy should be commensurate with the duration and severity of the diabetes, and other causes of sensorimotor polyneuropathy should be excluded. Longer nerve fibres are affected to a greater degree than shorter ones, because nerve conduction velocity is slowed in proportion to a nerve’s length.

The first clinical signs that usually develop is decrease or loss of vibratory and pinprick sensation over the toes. As disease progresses, the level of decreased sensation may move upward into the legs and then into the hands and arms, a pattern often referred to as ‘stocking and glove’ sensory loss. A glove–stocking distribution of numbness, sensory loss, dysaesthesia and night-time pain may develop. The pain can feel like burning, pricking sensation, achy or dull. Pins and needles sensation is common. Loss of proprioception, the sense of where a limb is in space, is affected early. These patients cannot feel when they are stepping on a foreign body, such as a splinter, or when they are developing a callous from an ill-fitting shoe. Consequently, they are at risk for developing ulcers and infections on the feet and legs.

Very severely affected patients may lose sensation in a shield distribution on the chest. Deep tendon reflexes are commonly hypoactive or absent, and weakness of small foot muscles may develop. More focal findings may be seen with injury to specific nerves as described above. Loss of motor function results in dorsiflexion, contractures of the toes and loss of the interosseous muscle function, and leads to contraction of the digits, so-called ‘hammer toes’. These contractures occur not only in the foot but also in the hand, where the loss of the musculature makes the hand appear gaunt and skeletal.